Quiets the hair-suppressing prostaglandin
Prostaglandin D2↓
Also searched as Prostaglandin D2.
There is no single direction to want. Blocking it is the point in balding scalp and would cost you sleep if it were systemic — which is exactly why the hair drugs target GPR44 specifically.
In depth
Prostaglandin D2 — one lipid signal with two receptors: DP1 in the brain, where it is the most potent sleep-promoting substance known, and DP2/GPR44 in the scalp, where it suppresses the hair growth phase.
What drives it
Calms histamine response increases it.
Lewis 1982, J Immunol 129:1627 — mast cells are an exceptionally rich source of prostaglandin D2, generated on IgE-dependent activation. PMID 6809826
What it drives
It reduces Hair.
Garza 2012, Sci Transl Med 4:126ra34 — prostaglandin D2 inhibits hair growth and is elevated (via PTGDS) in the bald scalp of men with AGA, acting through GPR44; this is the mediator luteolin suppresses. doi:10.1126/scitranslmed.3003122. Prostaglandin D2 synthase (PTGDS) is elevated at both mRNA and protein level in bald scalp compared with haired scalp of the same men with AGA, and PGD2 itself is correspondingly elevated. this is an expression difference between scalp regions — direction of causation is supported by the wider literature on PGD2/GPR44 inhibition of hair growth, but the observation itself is correlative. doi 10.1126/scitranslmed.3003122.
It increases Sleep.
PGD2 lives in the SOMNOGEN literature: prostaglandin D2 is the most potent endogenous sleep-promoting substance thus far reported. The pathway stands for the molecule rather than one of its jobs. Inhibitor abolishes sleep; delete the target and the inhibitor does nothing. A DP1 antagonist reduced sleep of rats by 30 percent. One lipid, two receptors, opposite things worth wanting — DP1 in brain gives sleep, DP2/GPR44 in scalp suppresses hair growth. That is why the balding drugs target GPR44 specifically, and why the pathway is drawn balanced rather than with a direction. It accumulates during prolonged wakefulness and circulates in CSF as a sleep hormone, produced by lipocalin-type PGD synthase in leptomeninges, choroid plexus and oligodendrocytes. doi 10.1111/j.1479-8425.2010.00470.x · PMID 19768929
It increases Sleep pressure.
The mechanistic step, drawn separately because PGD2 does not ACT on sleep neurons itself. PGD2 stimulates DP1 receptors and increases the local extracellular concentration of adenosine in the basal forebrain as a paracrine sleep-promoting molecule. And the handoff is proven by knockout: PGD2 increases the extracellular level of adenosine in wild-type but not DP-receptor knockout mice, and A2A-receptor deficiency attenuates the somnogenic effect of PGD2. Not complete HANDOFF: PGD2-induced sleep in mice is mediated by both adenosine A2A-dependent and A2A-independent systems — A2A knockouts lose the episode-duration effect but keep the episode-number effect. Which is why the Prostaglandin D2 → Sleep link is drawn as well as the Prostaglandin D2 → Adenosine A1 link, rather than routed entirely through it. doi 10.1038/aps.2016.140 · PMID 22647469
It increases Pattern hair loss.
Prostaglandin D2 synthase (PTGDS) is elevated at mRNA and protein level in bald scalp compared with haired scalp of the same men with AGA, and PGD2 itself is similarly elevated. PGD2 inhibited growth of explanted human hair follicles (P<0.001) and acts through GPR44, not PTGDR. A K14-Ptgs2 transgenic mouse develops alopecia, follicular miniaturization and sebaceous gland hyperplasia — all hallmarks of human AGA. the human limb is a bald-vs-haired comparison plus explant culture, not a treatment trial; the causal demonstration is murine. Garza 2012, Sci Transl Med 4(126):126ra34. PMID 22440736
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.